tbuckley/cabot-search huggingface dataset:
The first report of K-Umbrella Gastric Cancer Study: An open label, multi-center, randomized, biomarker-integrated trial for second-line treatment of advanced gastric cancer (AGC).
Authors: Sun Young Rha, Choong-kun Lee, Hyo Song Kim, Minkyu Jung, Hyunki Kim, Bae Woo Kyun, Dong-Hoe Koo, Hei-Cheul Jeung, Sook Ryun Park, In Gyu Hwang, Dae Young Zang, Hyun Woo Lee, Sejung Park, Jung Mo Nam, Hyun Cheol Cheol Chung
Journal: Journal of Clinical Oncology (2022)

4001 Background: To explore proper agents for AGC patients as 2nd-line treatment based on optimal biomarker, we conducted K-Umbrella GC study with standard of care (SOC) controlled umbrella trial design. Methods: HER2-negative AGC patients from 6 Korean cancer centers were centrally screened for druggable targets by IHC and in situ hybridization. Patients were randomized to the biomarker vs. control group with SOC as 4:1 ratio. In the biomarker group, patients were treated with specific targeted agents in combination with weekly paclitaxel; 1) EGFR 2+/3+ patients for pan-ERBB inhibitor (afatinib; EGFR cohort), 2) PTEN loss/null (H-score &lt;100) patients for PIK3Cβ inhibitor (GSK2636771; PTEN cohort), and 3) PD-L1+, dMMR/MSI-high, or EBV-related cases for anti-PD-1 inhibitor (nivolumab; NIVO cohort). Control group and NONE cohort in biomarker group without predefined biomarkers were treated with SOC (weekly Paclitaxel±Ramucirumab). Primary endpoint was PFS between control and biomarker groups. Secondary endpoints included efficacy and safety of each cohort. Results: Between Feb 2016 and Feb 2021, total 722 patients were centrally screened. 329 patients were enrolled and randomized to control group (n=63) or biomarker group (n=266; EGFR cohort n=67; PTEN cohort n=42; NIVO cohort n=54; NONE cohort n=103). With a median follow-up of 35 months (95%CI 26.1-55.3), median PFS and OS were 3.8 (95%CI 3.2-4.3) and 8.9 (95%CI 7.8-10.1) months for biomarker group and 4.1 (95%CI 3.0-4.8) and 8.7 months (95%CI 7.2-10.2) for control group. In control group, PTEN loss/null was poor prognostic marker; patients with PTEN loss/null (n=12) showed worse survival compared to PTEN intact patients (n=51) (mPFS, 2.8 vs 4.3 months, P=0.03; mOS, 8.7 vs 9.1 months), where other biomarkers showed similar prognosis. Afatinib for EGFR cohort or GSK2636771 for PTEN cohort did not show significant survival benefit compared to control group (Table). Among patients with immune-related biomarkers, addition of nivolumab showed durable survival benefit (mOS 12.0 vs 7.6 months, P=0.08) compared to SOC. Conclusions: Considering the characteristics of umbrella design with multiple biomarkers having different biological roles, biomarker group did not show the improved survival over control arm with these 3 drugs. For optimal biomarker-driven targeted agent applications, NGS-based biomarker driven K-Umbrella GC-2 study is ongoing. Clinical trial information: NCT02951091. [Table: see text]
Contemporary trends of systemic neoadjuvant and adjuvant intravesical chemotherapy for upper tract urothelial carcinomas undergoing minimally invasive or open radical nephroureterectomy: US-claims analysis on perioperative and health care costs outcomes
Authors: F. Del Giudice, V.U. Stefanie, A. Sciarra, S. Salciccia, M. Maggi, V. Canale, S. Flammia, P. Viscuso, M. Moriconi, M. Pecoraro, V. Panebianco, B.I. Chung
Journal: European Urology (2022)
Utility of bladder EpiCheck methylation test for the surveillance of bladder cancer patients treated with bacillus Calmette-Guérin
Authors: L. Mengual, M. Ingelmo-Torres, R. Carrasco, F.L. Roldan, M. Garcia, A. Alcaraz, L. Izquierdo, M.J. Ribal
Journal: European Urology (2022)
Treatment patterns and medical costs of metastatic breast cancer care in the United States.
Authors: Rachel Jaber Chehayeb, Annette Hood, Sarah Schellhorn Mougalian, Maryam B. Lustberg, Shi-Yi Wang, Rachel Adams Greenup, Lajos Pusztai, Natalia Kunst
Journal: Journal of Clinical Oncology (2022)

e18834 Background: Substantial advances in treatment of metastatic breast cancer (mBC) have led to changes in clinical practice and treatment costs in the United States in the past decade. We aimed to identify treatment patterns in mBC patients by subgroup and year after mBC diagnosis and associated costs from payer and societal perspectives. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database (1/2011-5/2021). We excluded cases that were male, had &lt; 6 months of follow up, no treatment data, no structured data within 90 days of diagnosis, participated in clinical trials, had non-breast invasive cancers, received therapies not used in mBC, had no data on human epidermal growth factor (HER2) and hormone receptor (HR) status. We classified patients into four subgroups: HER2-HR+, HER2+HR+, HER2+HR-, and Triple Negative (TNBC). We calculated anti-cancer and supportive drug costs at the patient level and mean costs by year after diagnosis for each subgroup. We used average wholesale prices (AWP, from McKesson Corporation) for payer perspective and Medicare prices (part B payment limit data, Part D Drug Spending Dashboard) for societal perspective. We estimated costs up to year 5 after diagnosis of mBC (&lt; 8% received treatment after year 5). Results: 15,215 patients met the criteria (64.41% non-Hispanic White, 66.85% HER2-HR+, 18.30% HER2+HR+, 5.27% HER2+HR-, 9.58% TNBC). AWP and Medicare cost estimates by year after diagnosis and subgroup are shown in Table. 334,812 for HER2+HR+, $284,609 for HER2+HR-, $104,774 for HER2-HR+, and $54,355 for the TNBC. We observed an increase in annual costs between years 2011-2021 in most subgroups. This increase was most substantial for HER2-HR+ patients. From 2011 to 2019 (most recent complete year 1 data is for patients diagnosed in 2019), annual Medicare treatment costs in year 1 increased from $12,986 to $80,563 for HER2-HR+, $99,997 to $156,712 for HER2+HR+, and $31,397 to $53,775 for TNBC. There was no increase in costs of treating HER2+HR- in year 1, but an increase in year 2 (from $90,427 to $129,690 between 2011-2019). Conclusions: mBC treatment costs vary significantly by receptor subtype and years after diagnosis. Annual costs increased over time. Costs were greatest for HER2+ and lowest for TNBC.[Table: see text]
EPCT-05. Phase Ib study of unesbulin (PTC596) in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) and high-grade glioma (HGG): A report from the COllaborative Network for NEuro-Oncology Clinical Trials (CONNECT)
Authors: Margot A Lazow, Patricia Baxter, Joseph Stanek, Adam Lane, Diana P Rodriguez, Shiva Senthil Kumar, James L Leach, Leonie Mikael, Christine Fuller, Daniel R Boué, Christopher R Pierson, Diana Thomas, John Breneman, Joshua Palmer, Xiao-Nan Li, Ralph Salloum, David Ashley, Peter de Blank, Eugene Hwang, Sarah E S Leary, Ashley Plant, Dorothy Crabtree, Mona Wahba, Marla Weetall, John Baird, Jeffrey Leonard, Clinton F Stewart, Elaine Mardis, Maryam Fouladi, Rachid Drissi
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The B-cell-specific Moloney murine leukemia virus integration site-1 (BMI-1) protein, implicated in self-renewal and DNA-damage signaling, is highly expressed in DIPG and HGG. Preclinically, BMI-1 modulation by unesbulin (PTC596 [which mediates hyperphosphorylation and subsequent degradation of BMI-1]) leads to DIPG/HGG cell proliferation blockade, mitotic abnormalities, and tumor cell sensitization to radiation-induced DNA damage. METHODS: This phase Ib study sought to determine the maximally tolerated dose/ recommended phase 2 dose (RP2D) of unesbulin administered concurrently with radiotherapy and adjuvantly in children with newly diagnosed DIPG or HGG. Patients were enrolled according to a Rolling-6 design and received oral unesbulin twice weekly during radiotherapy and as maintenance therapy. RESULTS: Twenty-seven patients enrolled (median age: 8.5 years [range: 2-18]), including 18 patients with DIPG and nine patients with HGG. Unesbulin was administered in capsule formulation in the first nine patients, then tablet formulation for subsequent patients. Within the capsule formulation group, three dose-limiting toxicities (DLTs) were observed in two patients on dose level 2 (grade 4 neutropenia). Within the tablet formulation group, four DLTs were experienced by three patients on dose level 2 (grade 3 ALT elevation, grade 3 dehydration/vomiting, grade 3 decreased ejection fraction, grade 4 neutropenia). Dose level 1 was declared the RP2D, and six additional patients enrolled in the expansion cohort at this dose without DLTs. Most common drug-related grade 3/4 toxicities were neutropenia (48%), leucopenia (35%), and elevated ALT (26%). Similar pharmacokinetic profiles were observed for capsule and tablet formulations, consistent with adult data. Survival outcomes and genomics results will be shared at time of presentation. CONCLUSIONS: The RP2D of unesbulin in children newly diagnosed with DIPG or HGG is 200mg/m2 twice weekly, concurrent with and following radiotherapy. The recently opened surgical cohort will assess intratumoral pharmacokinetics and inhibition of tumor BMI-1 signaling, with results forthcoming.
Mammary analog secretory carcinoma in adults: A systematic review.
Authors: Dawood Findakly, Kavitha Beedupalli
Journal: Journal of Clinical Oncology (2022)

e18076 Background: Mammary analog secretory carcinoma (MASC) is a rare malignant salivary gland tumor of the head and neck region that was first described by Skálová et al. in 2010. It histologically mimics breast secretory carcinoma and parotid acinic cell carcinoma, and characterized by ETV6-NTRK3 fusion gene. This review aims to investigate the clinicopathologic features, treatment, and outcomes of MASC in adults. Methods: PubMed search for MASC adults (18+ years) from data inception through 2021, pooled with a case from our institution. Kaplan-Meier analysis was used to plot survival curves. Results: Of the 254 included cases, female:male ratio 1.02:1 with a mean age at diagnosis (±SD, range) of 50.1 (±16.7, 18–86) years. In terms of location, 143 (56.3%) occurred in the parotid gland, 21 (8.3%) in the submandibular gland, 21 (8.3%) in the lip, 15 (5.9%) in the thyroid gland–all (100%) had a component of classical type papillary carcinoma, 15 (5.9%) were cutaneous, 13 (5.1%) in the buccal mucosa, 12 (4.7%) split between hard and soft palate, 4 (1.6%) in the nasal mucosa, 2 (0.8%) in the lung, and remaining 8 (3.1%) each in the conjunctiva, tongue, minor salivary gland, submaxillary gland, maxillary sinus, ethmoid sinus, upper esophagus, and mandible. Patients mostly presented with swelling or growing mass in 95.4% (out of which, 93.3% were painless), followed by a painful ulcer in 1.8%. Median tumor size was 1.9 cm (range 0.3cm–8.5cm). Median duration of symptoms at time of presentation was 12 (range 1-360) months. Tumors were T1 (49.7%), T2 (23.9%), T3 (20.3%), and T4 (6.1%), N0 (81.9%), N1 (10.7%), N2 (7.4%), M0 (97.4%), and M1 (2.6%). Most patients (70.7%) presented as early stage (I or II) which was associated with a high survival probability based on a log-rank test (p-value: 0.0007). All patients had surgical resection, mostly combined with neck dissection (ND) in11.4%, radiation (RT) in 7.8%, ND+RT in 4.7%, ND with platinum-based chemoradiation in 1.0%, and one case reported use of Crizotinib followed by Entrectinib with disease progression at 4.5 and 7 months, respectively. Among patients with reported outcomes, 92.2% were alive with a median follow-up of 26 (range 1-228) months, and 7.8% deceased with a median time-to-death of 29 (range 1-107) months. Eleven (4.3%) reported a high-grade MASC and 18.5% of patients lived for over five years after their diagnosis. Conclusions: Early stage was a notable predictor of higher survival probability in MASC patients. Its rarity, heterogeneity of clinical behaviors, and variable outcomes make it even more challenging. This review serves as real-world evidence to further our understanding of this rare entity and shed light on prospective clinical trial design.
Immunological signature of patients with thymic epithelial tumors.
Authors: Rocco Morra, Pietro De Placido, Erica Pietroluongo, Margaret Ottaviano, Marianna Tortora, Brigitta Mucci, Liliana Montella, Vitantonio Del Deo, Anna Maria Malfitano, Miriam Pirolo, Federico Mirra, Angelo Vaia, Vittoria D'Esposito, Daniela Terracciano, Sabino De Placido, Pietro Formisano, Giovannella Palmieri, Mario Giuliano
Journal: Journal of Clinical Oncology (2022)

8589 Background: Thymic epithelial tumors (TETs) are complex diseases frequently associated with immune disorders, including Good Syndrome (GS). Etiopathogenesis of immune dysregulations in TETs patients is still not totally explained. The aim of this study was to evaluate differences in immune cell phenotype, as well as in the serum expression levels of a panel of cytokines, chemokines, and growth factors in patients with TETs and GS with or without autoimmune disorders (AD). Methods: From May 2019 to June 2020, consecutive patients with TETs and GS were recruited at Rare Tumors Coordinating Center of Campania Region (CRCTR – Naples, Italy). We analyzed the immunophenotype from peripheral blood focusing on selected immune cell subsets (monocytes, neutrophils, eosinophils, CD4+T cells, CD8+T cells, B-cells, NK cells and NKT- cells, T regulatory cells) processed for blood cell count and immunophenotyping, according to the 8-color immunophenotyping kit and Treg detection kit (CD4/CD25/CD127), and a panel of cytokines, chemokines, and growth factors from peripheral blood serum screened with pre-formed kits by Bioplex multiplex. D’Agostino-Pearson normality test was used to evaluate whether the continuous data were normally distributed, and a two-tailed t-test for independent samples was used. p-values &lt; 0.05 were considered statistically significant. Results: Overall, 29 patients were enrolled [17 (58.6%) with and 12 (41.4%) without AD]. Sixteen patients (55.2%) were female and 13 patients (44.8%) were male. Tumor histology included thymoma in all the patients with AD, whereas there were 10 cases of thymoma and 2 of thymic carcinoma in the group of patients without AD. The analysis of leucocytes by blood cell count showed a statistically significant higher number of leucocytes, ascribable to T lymphocytes (p = 0.023), B lymphopenia (p = 0.003) and decrease of T regulatory cells (p = 0.009) in TET patients with AD, as compared with TET patients without AD. Moreover, TET patients with AD showed significantly higher circulating levels of IL-15 (p = 0.032), VEGF (p = 0.007), IP-10 (p = 0.013), GM-CSF (p = 0.042), IL-6 (p = 0.031), and MIP-1α (p = 0.017) with respect to TET patients without AD. Conclusions: To our knowledge, this is the first report describing a profound alteration in B and T lymphocytes in TET patients associated with AD. The observed differences may be potentially important in the clinical management of this complex disease. Additional studies are needed to better understand the immunophenotypic alterations in TETs patients.
Survival in N3 penile cancer: Does pelvic lymphadenopathy predict a worse prognosis than inguinal extra-nodal extension?
Authors: J. Churchill, A. Sachdeva, A. Issa, C. Jones, F. Azhar, I. Aneke, N.W. Clarke, M.W. Lau, V.K. Sangar, A.S. Parnham
Journal: European Urology (2022)
Clinicopathological significance of exosomal proteins CD9, CD63 and DNA mismatch repair proteins in prostate adenocarcinoma and benign hyperplasia
Authors: K. Folkmanis, E. Junk, E. Merdane, I. Folkmane, V. Folkmanis, I. Ivanovs, J. Eglitis, M. Jakubovskis, S. Laabs, S. Isajevs, V. Lietuvietis, M. Addali
Journal: European Urology (2022)
99m-technetium-psma radio-guided surgery to detect nodal metastases in prostate cancer patients undergoing radical prostatectomy and extended pelvic lymph node dissection: A phase 2 prospective, single-institution study
Authors: G. Gandaglia, E. Mazzone, A. Pellegrino, N. Fossati, A. Stabile, S. Scuderi, F. Barletta, R. Leni, D. Robesti, L. D'Ambrosio, L.M. Vitale, A.M. Samanes Gajate, M. Picchio, L. Gianolli, F. Montorsi, A. Briganti
Journal: European Urology (2022)
LGG-16. Retrospective and integrative analyses of molecular characteristics and their specific imaging parameters in pediatric grade 1 gliomas.
Authors: Marie Courant, Benoit Lhermitte, Eric Guerin, Agathe Chammas, Damien Reita, Consuelo Sebastia, Valérie Douzal, Flaviu Gabor, Alexandra Salmon, Julien Todeschi, Andres Hugo Coca, Florence Vincent, Natacha Entz-Werlé
Journal: Neuro-Oncology (2022)

Abstract Pediatric low-grade gliomas (PLGG) are the most common brain tumors diagnosed during childhood and represent a heterogeneous group associating variable molecular abnormalities. To go further and develop specific statistical patterns integrating altogether tumor molecular background, imaging features and patient outcome, a retrospective study was performed in a group of non-NF1 grade 1 PLGGs. So, 78 children, followed from 2004 to 2017, were retrospectively reported. Their therapeutic management comprised surgery or surgery plus chemotherapies (e.g., carboplatin and vincristine). In this population, radiological and molecular patterns were pooled statistically to be able to identify specific prognostic subgroups. Considering all 78 patients, 59 had only a surgical removal and 19 patients were treated with post-operative chemotherapy. Twelve progressions were reported in the partially resected and chemotherapeutic groups, whereas 4 deaths occurred only in the highly treated patients. As expected, PLGG with BRAF pV600E and/or CDKN2A loss exhibited poor outcomes. Nevertheless, we were able to evidence statistically significant associations between molecular characteristics and their specific imaging presentation on diagnostic and 24-week MRIs. In the chemo-treated patients, the molecularly good risk situations were significantly linked to the presence of a large tumor cyst at diagnosis (&amp;gt; 50% of the tumor volume (TV)) and the appearance during treatment of a higher cystic proportion that we called “cystic conversion”. So, additionally to the WHO prognostic molecular patterns, precise MRI characteristics (notably cystic part proportions onto TV) were associated to BRAF p.V600E PLGGs, as well as to the more frequent molecular KIAA1549-BRAF fused PLGGs. To summarize, absence on diagnostic MRI of cystic parts and/or cystic conversion at 6-month chemotherapy time point were significantly linked to a worst prognosis and response to treatment. In future studies, these imaging features might be considered as innovative prognostic markers to use during treatment.
The circadian immune system
Authors: Chen Wang, Lydia Kay Lutes, Coline Barnoud, Christoph Scheiermann
Journal: Science Immunology (2022)

The immune system is highly time-of-day dependent. Pioneering studies in the 1960s were the first to identify immune responses to be under a circadian control. Only in the last decade, however, have the molecular factors governing circadian immune rhythms been identified. These studies have revealed a highly complex picture of the interconnectivity of rhythmicity within immune cells with that of their environment. Here, we provide a global overview of the circadian immune system, focusing on recent advances in the rapidly expanding field of circadian immunology.
Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study
Authors: Maël Heiblig, Marcela A. Ferrada, Matthew T. Koster, Thomas Barba, Mathieu Gerfaud-Valentin, Arsène Mékinian, Henrique Coelho, Gaelle Fossard, Fiorenza Barraco, Lionel Galicier, Boris Bienvenu, Pierre Hirsch, Guillaume Vial, Anne Blandine Boutin, Joris Galland, Guillaume Le Guenno, Adrien Bigot, Kenneth J. Warrington, Tanaz A. Kermani, Peter C. Grayson, Bhavisha A. Patel, David B. Beck, Yvan Jamilloux, Pierre Fenaux, Pierre Sujobert
Journal: Blood (2022)
REDD1 is a gatekeeper of murine hematopoietic stem cell functions during stress responses
Authors: Vilma Barroca, Elia Henry, Nathalie Dechamps, Laurent Renou, Paul Chaintreuil, Rohan Kulkarni, Saiyirami Devanand, Arnaud Jacquel, Guillaume Robert, Patrick Auberger, Françoise Pflumio, Marie-Laure Arcangeli
Journal: Leukemia (2022)
Real world evidence for use of NACT in locally advanced external auditory canal cancer.
Authors: Rahul Kumar Rai, Vijay Maruti Patil, Vanita Noronha, Nandini Sharrel Menon, Saswata Saha, Mitali Alone, P. S. Pai, Sarbani Laskar, Kumar Prabhash
Journal: Journal of Clinical Oncology (2022)

e18000 Background: The management of very locally advanced external auditory canal cancers (LAEACC) is complicated, has a dismal prognosis and there is limited literature available for guidance. At our institute, we have offered neoadjuvant chemotherapy (NACT) to such patients. The objective of the current analysis was to study the outcomes and adverse events with this approach. Methods: We identified 16 patients with LAEACC over a period of 10 years (2010-2020) from the neoadjuvant chemotherapy (NACT) database of the Head and Neck department at our hospital. All patients were seen in a multidisciplinary clinic before and after NACT. Further local therapy was planned as per the response and ECOG PS of the patient. SPSS version 20 was used for analysis. Descriptive statistics were performed and Kaplan-Meier analysis was done to evaluate overall survival and progression-free survival. Results: Out of 16 patients enrolled in the study, 14 patients eventually received NACT. The median age was 59.5 years (27 - 83), the male to female ratio was 7:1 and the ECOG PS was 0-1 in 14 (87.5%) and PS 2 in rest. The regimen offered was a 2 drug regimen of taxane and platinum in 11 patients and a 3 drug regimen of TPF in (7.14%) patients. The median cycle received was 2. Post NACT 6 (42.85%) patients underwent surgery, 5 (35.71%) received radical CTRT and 3 (21.42%) patients received palliative treatment. The median progression-free survival was 1.67 years [95% CI (0.364 - 6.175)] while the median overall survival was 2.0 years [95% CI (0.455 - 6.175)]. Conclusions: Locally advanced EACC where upfront surgery is not feasible, NACT can be considered an option as patients receiving NACT have a 44.44% response rate and surgical resection rate of 42.8%.
A systematic review and meta-regression of placebo effect in chronic prostatitis/ chronic pelvic pain syndrome
Authors: A.O. Morozov, A. Bazarkin, D. Babaevskaya, M. Taratkin, V. Kozlov, A. Suvorov, L. Spivak, J. Mcfarland, G.I. Russo, D. Enikeev
Journal: European Urology (2022)
Histological comparison of buccal mucosa grafts for urethroplasty: Are inner cheek and sublingual area sharing the same properties and vascular supply?
Authors: F. Campos Juanatey, P. Calleja Hermosa, A. Azueta Etxebarria, S. Marcos Gonzalez, E. Fernandez Guzman, E. Alonso Mediavilla, N. Garcia Formoso, M. Sanchez Gil, J. Garcia Herrero, G. Azcarraga Aranegui, S. Rouco Villahoz, S. Zubillaga Guerrero, M. Dominguez Esteban, M.A. Correas Gomez, J.L. Gutierrez Baños
Journal: European Urology (2022)